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Biomedical subjects

A Bandeira

Publications and source records attributed to A Bandeira.

At least 55 records · Page 3Linked to original sources
PubMed1989

Preferential expansion of Ly-1 B and CD4- CD8- T cells in the polyclonal lymphocyte responses to murine T. cruzi infection.

Acute murine infection with T. cruzi results in polyclonal lymphocyte responses manifested by blast transformation of a large fraction of B, CD4+, and CD8+ cells. We describe here the finding of significant increases in the splenic representation of minor populations, Ly-1 + B cells and CD4-CD8- T cells. These lymphocyte populations might play an important role in the host response, as shown by T. cruzi infection of hosts that had been lethally irradiated and reconstituted with autologous bone marrow. Under these conditions, the splenic polyclonal PFC responses are nearly abrogated, and not restored by the transfer of syngeneic peritoneal cells which, however, reconstitute T15 idiotype production in the same hosts. Control levels of PFC responses, however, are reconstituted by transfer of syngeneic splenic T cells. Since bone marrow-reconstituted animals contain normal numbers of CD4+ and CD8+ T cells which are actually activated by infection, these results suggest the participation of other T cell populations in the host response to infection, as also suggested by the marked increases in T cell receptor gamma and delta messages detected in the spleen of infected animals. The implications of these findings in immunopathology of Chagas' disease are discussed.

Animals↗
PubMed1989

A model system for the analysis of B-cell activation and effector T-cell functions. T cell-dependent B-cell responses facilitated by anti-I-A antibodies.

We have attempted to develop an in vitro system where polyclonal B lymphocyte responses could be induced in 'antigen-like' conditions, that is, where surface immunoglobulin-dependent binding mediates interaction with a mitogen. Monoclonal anti-mu and anti-delta antibodies were covalently bound to lipopolysaccharide (LPS) and these complexes were shown to display mitogenic activity. Polyclonal plaque-forming cell (PFC) responses, however, were diminished in cultures stimulated by anti-mu-LPS (but not by anti-delta-LPS) indicating that 'anti-mu inhibition' of terminal B-cell differentiation also applies to 'specific' antibody responses. Moreover, the analysis of the functional activity of monoclonal antibodies to major histocompatibility complex (MHC) class II molecules revealed a surprising synergy between low, non-stimulatory concentrations of anti-mu-LPS (but not anti-delta-LPS) with anti-I-A antibodies. These responses are T-cell dependent and synergy with anti-mu-LPS conjugates can also be obtained with 'naturally' activated CD4+ cells isolated from normal donors. A model of molecular and cellular interactions was derived, which accounts for the present findings and is applicable in antigen-dependent lymphocyte collaboration.

Adjuvants, Immunologic↗
PubMed1989

Lymphoproliferative syndrome associated with c-myc expression driven by a class I gene promoter in transgenic mice.

We have produced transgenic mice carrying an H-2K/human c-myc fusion gene. In this construct, the human c-myc proto-oncogene expression is driven by the 5' flanking sequences (including promoter) of the class I H-2Kb gene, which have previously been shown to direct the expression of a marker gene, the human growth hormone (hGH), in most tissues of H-2K/hGH transgenic mice. Comparative analysis, by S1 nuclease mapping, of the H-2K and human c-myc gene expression in different organs of the H-2K/myc mice shows that exogenous c-myc and endogenous H-2K expression is found in most organs examined. However, the liver is a notable exception, for here c-myc expression is very weak. The exogenous c-myc expression is maximal in lymphoid organs of all H-2K/myc transgenic strains. One strain, H-2K/myc 27, hereditarily develops a lymphoproliferative syndrome which eventually leads to death. The H-2K/myc 27 lymphoid tissues are profoundly abnormal: pre-B cells as well as mature B cells are underrepresented in the bone marrow but the thymus as well as lymph nodes are largely infiltrated by B cells. Moreover, in the thymus, the proportions of the different thymic cell populations are altered. However, in the other H-2K/myc transgenic strains, even in those expressing a comparable or even higher level of myc, no pathology has been observed over a period of 20 months. Our results, therefore, demonstrate that constitutive enforced c-myc expression might disturb lymphocyte development, but does not directly lead to malignancy.

Animals↗
PubMed1988

Back-stimulation of B lymphocytes binding to helper T cell surface antigens.

Helper T cells directed to B cell surface determinants activate their "targets" into polyclonal antibody production in vitro and in vivo, but B cells which bind to epitopes on the helper cell surface are preferentially induced. Furthermore, "anti-helper" B cell activation also occurs by "back-stimulation", that is even when the responding B lymphocytes are not specific targets for the inducing helper cells, as long as these are simultaneously activated by appropriate interactions with presenting cells. In our experimental systems, this is the only condition where "bystander" activation can be recorded. These findings suggest mechanisms of auto-antibody production associated with unrelated helper cell activity in vivo.

Animals↗
PubMed1988

A phenotypic and functional analysis of long-lived B and T lymphocytes.

The lymphocyte composition of spleen, lymph nodes, bone marrow, and thymus of mice submitted to hydroxyurea treatments for four consecutive days was studied. The treatment selects for small lymphocyte populations that represent between 4 and 20% of control numbers in the various organs. Spleen and bone marrow contain the same B cell population with a low IgM, high IgD, low I-E phenotype, which respond to LPS at control clonal frequencies. The T cell compartment is equally depleted, and the lymphocytes remaining contain frequencies of clonable cells in response to mitogens and IL-2 that are comparable to those detected in normal spleen cells. Overall, the results suggest that only a minor fraction of all lymphocytes in a normal young adult mouse have life spans longer than 4 days.

Animals↗
PubMed1988

Limiting dilution analysis of interleukin-2-producing mature T cells. Interleukin 2 secretion is an exclusive property of L3T4+ lymphocytes.

Evaluation of lymphokine production by individual activated T cells is necessary to characterize their growth requirements. We have studied interleukin 2 (IL-2) secretion by mature T lymphocytes using a high resolution assay system with the following characteristics: (a) a threshold of IL-2 detection 25 times lower than classic IL-2 titration; (b) the ability to discriminate between IL-2 and IL-4 activities; (c) absence of 'in situ' IL-2 absorption; (d) IL-2 production revealed at the single cell level. By this method an average of 10% of spleen cells, and 75% of L3T4+ cells were detected as producers in a concanavalin A (Con A)-dependent T cell activation system. Our results also suggest the complete restriction of IL-2 secretion to cells with this phenotype. Therefore, factors other than IL-2 must play a major role in Lyt 2+ mitogen-driven, helper-independent T cell proliferation.

Animals↗
PubMed1987

"In vivo" activated splenic T cells are refractory to interleukin 2 growth "in vitro".

Naturally activated T lymphocytes present in normal mouse spleen were studied for direct reactivity to interleukin 2 (IL 2) and for binding of anti-IL 2 receptor (IL 2R) antibodies or radiolabeled IL 2. The majority of large-sized splenic T lymphocytes are IL 2R-; thus, at the most one third of large L3T4+ T cells and of large Lyt-2+ T lymphocytes bind (weakly) anti-IL 2R antibodies; furthermore, most IL 2R+ cells in the normal spleen are actually Lyt2-, L3T4-. Total large splenic lymphocytes do not express more than an average of 150 high-affinity IL 2R/cell. Such cell populations, as well as large T cells enriched from them, failed to proliferate exponentially in the presence of recombinant IL 2, but did not suppress the IL 2-dependent proliferative responses of small T cells activated in the same cultures. In vivo activation of small T cells, in concanavalin A-treated irradiated syngeneic hosts, also results in refractoriness to growth in recombinant IL 2. In addition, these cells remain insensitive to ligands such as concanavalin A, phorbol myristate acetate and ionomycin, in the presence or absence of IL 2. These results question the role of IL 2 as a growth factor of in vivo activated splenic T lymphocytes, or else indicate that most of these are terminally differentiated cells.

Animals↗
PubMed1987

Sporadic idiotypic cross-reactivities between antibodies and T helper cells: one example of aleatory expression of T cell idiotypes.

Idiotypic cross-reactivities between T and B cell receptors have been taken in the past to suggest VH-gene expression by both types of lymphocytes. More recently, after the molecular characterization of TcR, those observations were reinterpreted to indicate idiotypic network regulation, operating to select cross-reactive idiotypes in both B and T cell compartments. In support of these views, it has been shown that T cell expression of idiotypes is controlled by IgH-linked genes and markedly altered in B cell-deprived mice, and that T cells "learn" idiotype expression from the B cell compartment in the first few weeks of life. In most of these studies, aleatory idiotype cross-reactivities have not been sufficiently considered. Given the large diversity of antibodies and TcR, and the degeneracy of antibody-ligand interactions, it could be expected that a (monoclonal) anti-idiotypic reagent prepared against an antibody idiotope will always "cross-react" with some TcR variable regions. If these will be "major" T cell clonotypes, situations of idiotype sharing by B and T cells can be found which indicate neither VH-gene expression by T cells nor idiotypic network regulation. We report here one example of such aleatory expression of antibody idiotypes by T lymphocytes. A monoclonal anti-idiotypic antibody directed to anti-TNP antibodies of BALB/c mice specifically inhibits the growth and effector activity of C57BL/6 anti-NP-self helper T cells, while failing to interact with either BALB/c anti-NP-self or C57BL/6 anti-TNP-self helper cells. The clonotypic nature of these interactions could also be demonstrated by the specific induction of IL-2 production in the appropriate helper T cells by the anti-idiotypic antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Immunocompetent autoreactive B lymphocytes are activated cycling cells in normal mice.

Frequencies of B cell clonal precursors producing antibodies that react with mouse thyroglobulin, mouse erythrocytes, beef hemoglobin, KLH, and sheep erythrocytes were determined by limiting dilution analyses among small, resting lymphocytes, and among large activated cells from normal adult mice. While frequencies of clones reacting with external antigens were equally distributed in large and small B cells, most, if not all, autoreactive B lymphocytes were found in the large cell fraction. Analysis of antithyroglobulin hybridomas isolated from normal mice revealed dissociation constants ranging from 10(-6) to 5-6 X 10(-7). Treatment of normal donors with antimitotic drugs dramatically decreases the frequencies of autoreactive B cells, but not those of B lymphocytes reacting with external antigenic molecules. Taken together, these experiments show that immunocompetent, autoreactive B lymphocytes are activated and cycling cells in the peripheral lymphoid tissues of normal individuals.

Animals↗
PubMed1986

The role of immunoglobulin receptors in "cognate" T-B cell collaboration.

The functional effects of anti-Ig antibodies have been investigated, using an experimental system where B cell activation is brought about by direct and specific interactions with T helper (Th) cells without participation of surface Ig receptors on the responding B cell. We have used Th cell lines and clones directed to class II major histocompatibility complex antigens of the responding B cells, and titrated into cooperative cultures either purified rabbit anti-mouse mu, or monoclonal mouse anti-delta antibodies. Both types of antibodies greatly enhanced B lymphocyte responses to suboptimal concentrations of functionally efficient Th cells, while they had no effect in cultures containing optimal Th:B cell ratios. In contrast, helper activity by low efficiency Th was, at all Th:B cell ratios, enhanced by appropriate concentrations of anti-Ig antibodies. Anti-Ig effects were exclusively observed when B cells were the targets for "cognate" recognition by Th cells. We conclude that ligand binding to surface Ig receptors on resting B cells fails, in our experimental conditions, to overcome "linked" collaboration, but it greatly facilitates productive Th-B cell interactions. Whatever the mechanisms underlying this facilitation, the observations imply roles of surface Ig in Th-dependent B lymphocyte activation other than either passive "focusing" of antigen or activation into reactivity to soluble, unspecific factors.

Animals↗
PubMed1986

The basis for major histocompatibility complex (MHC) and immunoglobulin gene control of helper T cell idiotopes.

BALB/c helper T cells, prepared against 2,4,6-trinitrophenyl (TNP)-derivatized syngeneic spleen cells, fail to recognize other hapten modifications [(4-hydroxy-3-nitrophenyl)acetyl, fluorescein isothiocyanate] of syngeneic cells, as well as TNP-derivatized cells from major histocompatibility complex-congenic donors. T helper cell interactions with "presenting" cells and "target" B lymphocytes are inhibited by monoclonal antibodies directed either to the hapten or to I-A molecules on target cells. Helper activity is also inhibited by monoclonal anti-idiotypic antibodies directed to an idiotope expressed by the TNP-binding myeloma protein MOPC460, but not by soluble TNP-protein conjugates. The study of congenic mouse strains revealed that while the fine specificity of TNP recognition and the quantitative levels of M 460 idiotope expression are I-A linked, the expression of the M 460 idiotope by helper cells is controlled by IgCh-linked genes. Absence of anti-idiotope inhibition of helper cells prepared in anti-mu-suppressed mice suggests, however, that immunoglobulin idiotype expression by T cells results from network interactions selecting available lymphocyte repertoires which operate before antigenic stimulation.

Animals↗
PubMed1986

Functional and biochemical evidence for the recognition of T cell receptors by monoclonal antibodies to an immunoglobulin idiotype.

Sharing of "idiotypes" by T and B cells with similar nominal specificities has been extensively reported in functional assays. The recent molecular characterization of T cell receptors has led to the suggestion that such idiotypic mimicries could result from "network" selection of available T cell repertoires. Alternatively, the validity of the conclusions taken from those functional assays could be questioned. We have now used an experimental system where recurrent expression of antibody idiotypes by T helper cells requires "learning" from the B cell/antibody compartment, and show here that the idiotypic determinants in question are indeed associated with T cell receptor molecules. A monoclonal antibody (F6(51)) directed to an idiotope of the TNP-binding BALB/c myeloma protein MOPC460 specifically inhibits antigen-dependent proliferation and helper activity of BALB/c anti-TNP-BALB/c helper T cells. The anti-idiotypic antibodies also induce IL-2 production by these helper cells and precipitate a surface molecule with characteristics of T cell receptor. We conclude that, in this particular system, T cell receptors and antibodies of similar nominal specificities share idiotypic determinants.

Animals↗
PubMed1985

Different functional subsets of cultured murine T cells express characteristic levels of adenosine deaminase activity.

The level of adenosine deaminase (ADA) activity in mouse T-lymphocyte cultures was studied under different growth-supporting conditions and in mixed lymphocyte culture-derived long-term T-cell lines and clones. Early after the initiation of in vitro culture, the levels of ADA (2000 U/mg) were similar in bulk cultures either depleted or not depleted in Lyt-2+ T cells. Enrichment for cytolytic T lymphocytes (CTL) obtained by addition of exogenous interleukin 2 (IL-2), was accompanied by a net decrease of ADA activity (110 +/- 15 U/mg). All the tested CTL-A lines derived from such cultures were also characterized by a low or undetectable level of this enzyme (at best 160 +/- 70 U/mg) as previously observed. In contrast, "Lyt-2-" T-cell bulk cultures grown, without addition of exogenous IL-2, in the presence of gamma-irradiated H-2d stimulators maintained a constant level of ADA activity (1770 +/- 340 U/mg) for at least 3 months. Functionally distinct types of Lyt-2- T-cell lines were also analyzed: T-cell lines competent to activate B lymphocytes to growth and terminal maturation as well as others devoid of detectable functions showed a stable ADA level comparable to that expressed by the original bulk culture 1685 +/- 620 U/mg). The present results demonstrate that, like tumor cell lines, most normal T lymphocytes express a high level of ADA activity in culture, which strongly suggests that the low level of ADA activity exhibited by CTL is a characteristic of this functional subset.

Adenosine Deaminase↗